Investigation of the Expression Pattern and Functional Role of miR-10b in Intestinal Inflammation

SIMPLE SUMMARY: MicroRNAs (miRNAs) play a vital role in maintaining the homeostasis of the intestinal immune system, and dysregulation of miRNAs expression has been linked to several inflammatory diseases. Although miRNAs possess remarkable potential as molecular markers for monitoring diseases and disorders, their implications for animal health and welfare in livestock remain elusive. In the swine industry, weaning is the most challenging period for piglets, associated with a peak of intestinal immune activation and intestinal epithelium injury. Thus, it is interesting to identify suitable miRNAs as biomarkers for monitoring weaning-related disorders during the suckling-to-weaning transition in piglets and to investigate the potential of them being used as anti-inflammatory strategies for alleviating stress. This study has revealed a distinctive miR-10b expression pattern in the intestinal tissue of piglets following weaning and a critical role for miR-10b in immune regulation using a murine colitis model. These findings may provide new approaches for potential future interventions for swine health management. ABSTRACT: Implications of miRNAs for animal health management in livestock remain elusive. To identify suitable miRNAs as monitoring biomarkers, piglets were randomly selected for sampling on days 0, 1, 3, 7, and 14 post-weaning. The results show that miR-10b levels in the villus upper cells of the jejunum on days 3 and 7 were significantly lower than that on day 14 post-weaning and reduced by approximately 30% on day 3 and 55% on day 7 compared to day 0. In contrast, miR-10b in crypt cells decreased by approximately 82% on day 7 and 64% on day 14 compared with day 0. Next, miR-10 knockout mice and wild-type mice were subjected to dextran sulfate sodium (DSS) for 7 days. The findings demonstrate that mice lacking miR-10b were more susceptible to DSS administration, as demonstrated by worse survival, greater weight loss, more severe tissue damage, and increased intestinal permeability. Moreover, the increased disease severity was correlated with enhanced macrophage infiltration, coincident with significantly elevated pro-inflammatory mediators and immunoglobulins. Bioinformatic analysis further reveals that the enriched pathways were mainly involved in host immune responses, and Igtp was identified as a potential target of miR-10b. These findings may provide new strategies for future interventions for swine health and production.